title: The biocompatibility and biofilm resistance of implant coatings based on hydrophilic polymer brushes conjugated with antimicrobial peptides.
abstract: Bacterial colonization on implant surfaces and subsequent infections are one of the most common reasons for the failure of many indwelling devices. Several approaches including antimicrobial and antibiotic-eluting coatings on implants have been attempted; however, none of these approaches succeed in vivo. Here we report a polymer brush based implant coating that is non-toxic, antimicrobial and biofilm resistant. These coating consists of covalently grafted hydrophilic polymer chains conjugated with an optimized series of antimicrobial peptides (AMPs). These tethered AMPs maintained excellent broad spectrum antimicrobial activity in vitro and in vivo. We found that this specially structured robust coating was extremely effective in resisting biofilm formation, and that the biofilm resistance depended on the nature of conjugated peptides. The coating had no toxicity to osteoblast-like cells and showed insignificant platelet activation and adhesion, and complement activation in human blood. Since such coatings can be applied to most currently used implant surfaces, our approach has significant potential for the development of infection-resistant implants.
authors.affiliation: Centre for Blood Research and the Department of Pathology and Laboratory Medicine, 2350 Health Sciences Mall, University of British Columbia, Vancouver, BC V6T1Z3, Canada.
authors.forename: Guangzheng
authors.initials: G
authors.lastname: Gao
authors.forename: Dirk
authors.initials: D
authors.lastname: Lange
authors.forename: Kai
authors.initials: K
authors.lastname: Hilpert
authors.forename: Jason
authors.initials: J
authors.lastname: Kindrachuk
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Zou
authors.forename: John T J
authors.initials: JT
authors.lastname: Cheng
authors.forename: Mehdi
authors.initials: M
authors.lastname: Kazemzadeh-Narbat
authors.forename: Kai
authors.initials: K
authors.lastname: Yu
authors.forename: Rizhi
authors.initials: R
authors.lastname: Wang
authors.forename: Suzana K
authors.initials: SK
authors.lastname: Straus
authors.forename: Donald E
authors.initials: DE
authors.lastname: Brooks
authors.forename: Ben H
authors.initials: BH
authors.lastname: Chew
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
authors.forename: Jayachandran N
authors.initials: JN
authors.lastname: Kizhakkedathu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D018441:Biofilms / Q000254:growth & development*; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D020099:Coated Materials, Biocompatible / Q000009:adverse effects*; D005260:Female; D006801:Humans; D018625:Microscopy, Atomic Force; D010455:Peptides / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects; D011108:Polymers / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D019736:Prostheses and Implants / Q000009:adverse effects* / Q000382:microbiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000900:Anti-Bacterial Agents; D020099:Coated Materials, Biocompatible; D010455:Peptides; D011108:Polymers